Overview
Pyruvate dehydrogenase deficiency (PDH deficiency, also known as pyruvate dehydrogenase complex deficiency or PDCD) is a rare inborn error of mitochondrial energy metabolism caused by deficient activity of the pyruvate dehydrogenase complex (PDC). This enzyme complex is essential for converting pyruvate into acetyl-CoA, a critical step linking glycolysis to the citric acid cycle for cellular energy production. When this complex is deficient, cells—particularly in the brain—cannot efficiently generate energy through aerobic metabolism, leading to lactic acid accumulation in the blood and cerebrospinal fluid. The disease primarily affects the central nervous system, as the brain is highly dependent on aerobic glucose metabolism. Key clinical features include lactic acidosis, developmental delay, intellectual disability, seizures, hypotonia (low muscle tone), ataxia (poor coordination), and structural brain abnormalities such as agenesis or hypoplasia of the corpus callosum, ventriculomegaly, and cerebral atrophy. Severity ranges widely, from fatal neonatal lactic acidosis to milder forms presenting with episodic ataxia or developmental delay in childhood. Males tend to be more severely affected than females when the X-linked form is involved. The most common cause is mutations in the PDHA1 gene on the X chromosome, which encodes the E1-alpha subunit of the PDC. However, mutations in genes encoding other subunits (PDHB, DLAT, DLD, PDHX) follow autosomal recessive inheritance. Treatment options are limited but include a ketogenic diet, which provides an alternative fuel source (ketone bodies) that bypasses the need for PDC activity. Thiamine (vitamin B1) supplementation may benefit some patients with thiamine-responsive forms. Dichloroacetate has been used to reduce lactic acid levels, though its long-term efficacy and safety remain under investigation. Despite treatment, neurological outcomes are often poor, particularly in severe neonatal-onset cases.
Also known as:
Clinical phenotype terms— hover any for plain English:
Variable
Can be inherited in different ways depending on the underlying gene
Variable
Can begin at different ages, from infancy through adulthood
FDA & Trial Timeline
4 eventsAssistance Publique - Hôpitaux de Paris — PHASE2
Jirair Krikor Bedoyan — PHASE1
Saol Therapeutics Inc — PHASE3
University of Pittsburgh
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
No FDA-approved treatments are currently listed for Pyruvate dehydrogenase deficiency.
4 clinical trialsare actively recruiting — trials can provide access to cutting-edge therapies.
View clinical trials →Rare Disease Specialist
Treatment Centers
8 centersChildren's Hospital of Orange County
📍 Orange, California
👤 Richard Neibeger, MD
Children's Hospital of Philadelphia
📍 Philadelphia, Pennsylvania
👤 Study Director
👤 Richard Neibeger, MD
Children's National Medical Center
📍 Washington D.C., District of Columbia
👤 Richard Neibeger, MD
University of Florida
📍 Gainesville, Florida
👤 Richard Neibeger, MD
Stanford University
📍 Palo Alto, California
👤 Richard Neibeger, MD
Seattle Children's Hospital
📍 Seattle, Washington
👤 Study Director
👤 Richard Neibeger, MD
University of Utah
📍 Salt Lake City, Utah
👤 Anthony A. Amato, MD
👤 Richard Neibeger, MD
Baylor College of Medicine
📍 Houston, Texas
👤 Richard Neibeger, MD
Travel Grants
No travel grants are currently matched to Pyruvate dehydrogenase deficiency.
Community
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Start the conversation →Latest news about Pyruvate dehydrogenase deficiency
Disease timeline:
New recruiting trial: Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency Patients With Glycerol Phenylbutyrate (RAVICTI)
A new clinical trial is recruiting patients for Pyruvate dehydrogenase deficiency
New recruiting trial: Triheptanoin for Children With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency
A new clinical trial is recruiting patients for Pyruvate dehydrogenase deficiency
New trial: Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
Phase PHASE3 trial recruiting. Dichloroacetate (DCA)
Caregiver Resources
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Mental Health Support
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Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Common questions about Pyruvate dehydrogenase deficiency
What is Pyruvate dehydrogenase deficiency?
Pyruvate dehydrogenase deficiency (PDH deficiency, also known as pyruvate dehydrogenase complex deficiency or PDCD) is a rare inborn error of mitochondrial energy metabolism caused by deficient activity of the pyruvate dehydrogenase complex (PDC). This enzyme complex is essential for converting pyruvate into acetyl-CoA, a critical step linking glycolysis to the citric acid cycle for cellular energy production. When this complex is deficient, cells—particularly in the brain—cannot efficiently generate energy through aerobic metabolism, leading to lactic acid accumulation in the blood and cerebr
Are there clinical trials for Pyruvate dehydrogenase deficiency?
Yes — 4 recruiting clinical trials are currently listed for Pyruvate dehydrogenase deficiency on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat Pyruvate dehydrogenase deficiency?
2 specialists and care centers treating Pyruvate dehydrogenase deficiency are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.